Scott Eggener

M.D.

University of Chicago

Associate Professor of Surgery

PLCO (Learn more about this study)

PLCO-285

Jul 14, 2017

Impact of screening and management strategies on the development of metastatic disease in the PLCO Prostate Cancer Screening Trial

As advances continue in the management of prostate cancer (PCa), the economic burden continues to rise. The estimated national annual cost of PCa care by the year 2020 is $16.3 billion (Mariotto et al, J Natl Cancer Inst, 2011), with the majority of these costs incurred through the treatment of metastatic disease (Andronis et al, BJU Int, 2017; Armstrong et al, Curr Med Res Opin, 2017; Pilon et al, J Med Econ, 2016). Delay or prevention of metastases carries substantial favorable financial implications.

The Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial was one of two large scale randomized trials evaluating PCa screening in asymptomatic men. The primary endpoint was PCa-specific mortality (PCSM). Secondary endpoints included PCa incidence, PCa stage, Gleason grade, harms of screening, compliance, and all-cause mortality. Due to the significant contamination of the control arm, with ~90% undergoing some degree of PCa screening (Pinsky et al, Cancer, 2017; Shoag et al, N Engl J Med, 2016), the PLCO trial is largely considered a trial of organized vs opportunistic screening. While it may not have served its original purpose, it does contain extremely valuable clinical information. Metastatic disease was not a primary or secondary endpoint. However, this data is available in the PLCO dataset but has yet to be reported.

Analysis of metastatic disease in another large PCa screening trial, The European Randomized Study of Screening for Prostate Cancer (ERSPC), showed PSA-based screening significantly reduced the risk of developing metastases (Schröder et al, Eur Urol, 2012; Buzzoni et al, Eur Urol, 2015). Furthermore, ad hoc analysis revealed biopsy Gleason score and number of positive biopsy cores were independent predictors of developing metastases (Roemeling et al, Cancer, 2006).

We seek to evaluate the characteristics of men who are diagnosed with metastatic PCa at the time of initial diagnosis or treatment, as well as the impact of various screening and management strategies. This information will help describe the natural history of metastatic PCa in a screen-detected PCa population, potentially benefiting patients who are found to have early recognition of factors highly predictive of developing metastatic disease. All men diagnosed with PCa during the study will be included. We will include all men independent of randomization arm since the natural history of screen-detected PCa can be ascertained from both organized and opportunistic screening.

Specific Aim 1: Compare organized and opportunistic screening on rates of detecting metastatic disease.
The impact of different screening strategies is of great importance to patients and clinicians. All men diagnosed with PCa through screening with PSA or DRE will be included, independent of randomization arm. Metastatic and nonmetastatic PCa patients will be compared. We hypothesize there will be no difference in rates of metastatic disease between organized and opportunistic screening arms.

Specific Aim 2: Determine the characteristics of men diagnosed with metastatic PCa at the time of initial diagnosis or treatment.
Screening intensity, indication for biopsy, age-adjusted PSA level, and cancer-specific data from the diagnostic biopsy may all influence the likelihood of metastatic disease. Our proposed analyses will highlight the natural history of newly diagnosed metastatic PCa in a screen-detected PCa population, potentially benefiting patients identified with high-risk characteristics. We will compare men with metastatic disease to those with nonmetastatic disease. We hypothesize age-adjusted PSA level at study entry, PSA at biopsy, biopsy Gleason score, and number of positive biopsy cores will be independent predictors of metastasis.